title: Mitochondrial retinal dystrophy associated with the m.3243A>G mutation.
abstract: OBJECTIVE
  To describe the spectrum of retinal abnormalities associated with the m.3243A>G mutation in the mitochondrial MTTL1 gene and to analyze putative correlations among the severity of retinal abnormalities, disease severity in other organ systems, and heteroplasmy levels.
  
  
  METHODS
  Observational, cohort-based, cross-sectional study.
  
  
  METHODS
  Twenty-nine patients carrying the m.3243A>G mutation.
  
  
  METHODS
  Extensive clinical examinations, including visual acuity testing, indirect ophthalmoscopy, color fundus photography, fundus autofluorescence (FAF), high-resolution optical coherence tomography (OCT), and central visual field analysis. In selected patients, Goldmann perimetry, fluorescein angiography, full-field electroretinography (ERG) and electro-oculography (EOG), and color vision testing were performed. Heteroplasmy levels of the m.3243A>G mutation were measured in leukocytes, urinary epithelial cells (UECs), and buccal mucosa. The Newcastle Mitochondrial Disease Adult Scale (NMDAS) score was measured for all patients.
  
  
  METHODS
  Age at onset, visual acuity, fundus appearance, FAF, OCT findings, systemic disease features, heteroplasmy levels, and NMDAS scores.
  
  
  RESULTS
  Twenty-five of the 29 mutation carriers (86%) had retinal abnormalities that could be classified into 4 grades. Six patients (21%) had grade 1 retinal dystrophy with fine pigment abnormalities that were clearly visible with FAF and fluorescein angiography. Eleven patients (38%) had grade 2 abnormalities that were characterized by yellowish or mildly pigmented deposits in the early stage; in advanced grade 2, these pigment changes encompassed the entire macula and often encircled the optic disc. Six patients (21%) had grade 3 disease in which profound chorioretinal atrophy was present outside the fovea. Two patients (7%) with retinal abnormalities had grade 4 disease, in which the fovea was affected by atrophy, with marked loss of visual acuity. The grade of mitochondrial retinal dystrophy correlated significantly with both age (r = -0.483, P = 0.008) and visual acuity (r = -0.614, P < 0.001), whereas no correlation was observed with heteroplasmy level or overall disease involvement.
  
  
  CONCLUSIONS
  Mitochondrial retinal dystrophy associated with the m.3243A>G mutation has specific characteristics that can be classified into 4 grades based on the findings on ophthalmoscopy, FAF, and OCT. However, because the maternal inheritance pattern can be masked and the systemic disease associations can be variable or even absent, the disease may be misdiagnosed.
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Nijmegen, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Laat
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Nijmegen, The Netherlands.
authors.forename: Jan A M
authors.initials: JAM
authors.lastname: Smeitink
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Internal Medicine, Nijmegen, The Netherlands.
authors.forename: Mirian C H
authors.initials: MCH
authors.lastname: Janssen
authors.affiliation: Radboud University Nijmegen Medical Centre, Institute of Ophthalmology, Nijmegen, The Netherlands.
authors.forename: Jan E E
authors.initials: JEE
authors.lastname: Keunen
authors.affiliation: Radboud University Nijmegen Medical Centre, Institute of Ophthalmology, Nijmegen, The Netherlands; Nuffield Laboratory of Ophthalmology and Oxford Eye Hospital Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. Electronic address: cjfboon@hotmail.com.
authors.forename: Camiel J F
authors.initials: CJF
authors.lastname: Boon
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004585:Electrooculography; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D009887:Ophthalmoscopy; D017354:Point Mutation; D012356:RNA, Transfer, Leu / Q000235:genetics*; D058499:Retinal Dystrophies / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu